Our studies on the effect of methadone on the mother and fetus during gestation showed that treatment of female rats with daily doses of methadone of 7.5 mg/kg or less had no significant effect on the weight gain of the mother during the gestation period. There did, however, appear to be a dose related effect on the number of mothers dying during gestation as well as the number of live babies born. The mothers on low doses usually had a greater percentage of babies born alive and were more successful in carrying them through the first three weeks of life. Time course distribution studies demonstrated that methadone enters the fetal system just about as rapidly as it did the various maternal systems. Regardless of the route of administration (oral, Sub Q or IP) the methadone content of the fetal brain was 2 to 3 times as great as the methadone content of the maternal brain. In in vitro metabolism studies using hepatic microsomal preparations, we found that male rats N-demethylate methadone twice as fast as female rats and that non-pregnant female rats tend to N-demethylate methadone faster than pregnant rats while fetal rats are completely devoid of N- demethylating activity. Acute and chronic methadone treatment of the animals prior to sacrifice had no effect on metabolism in female rats but acute treatment caused a significant increase in metabolic activity in male rats.